The proposed Career Development Award project will provide the Candidate, Timothy A. Pritts, MD, PhD, a vehicle to attain full independence as a scientific investigator. Dr. Pritts'immediate and long term research goals are to become an independent surgeon scientist investigating the pathophysiology of hemorrhagic shock and resuscitation. The proposed research project involves hemorrhagic shock, a major cause of death and disability. Recent innovations in clinical care have been proposed as an attempt to improve immediate survival. Termed "damage control resuscitation," these strategies emphasize liberal transfusion of plasma and red blood cells. Early retrospective data suggest that increasing ratios of plasma to red blood cells leads to decreased immediate mortality in trauma patients but may allow subsequent death from multiple organ failure. To date, there are no studies examining the impact of damage control resuscitation strategies, as compared to traditional resuscitation, on subsequent development of SIRS, organ failure, and death. The proposed studies will use a murine model of hemorrhagic shock and resuscitation to directly compare resuscitation with crystalloid fluids, whole blood, and varying ratios of plasma to red blood cells on the development of systemic inflammation, organ failure, and death. The Career Development Plan will involve active mentoring by Alex Lentsch, PhD, as well as oversight by an advisory committee, diminution of clinical and administrative activities, and additional training in immunology. The research environment in the Department of Surgery is outstanding, with well equipped facilities and all necessary equipment to complete the proposed experiments. Dr. Pritts enjoys the complete support of his Chair, his Division Director, and the Department. PUBLIC HEALTH RELEVANCE: Hemorrhagic shock is a major cause of death in injured patients. Strategies to improve resuscitation and survival from hemorrhagic shock are evolving. The proposed experiments will increase understanding of the mechanisms of different resuscitation strategies for patients who are victims of hemorrhagic shock.